The proposed research program involves an extensive study of cyclic AMP-dependent chloride secretion by rabbit colon, in vitro, which will include (a) evaluation of a model for active chloride secretion elicited by cyclic AMP which is suggested by our preliminary observations; (b) studies of the requirement for serosal Na in the Cl secretory process; (c) determination of the unidirectional influx of Cl from serosal solution into the epithelial cells; (d) studies of the effects of pharmacologic agents on chloride secretion; (e) studies of the mechanism of Na transport which appears to be involved in Cl secretion; and (f) studies of the effect of cyclic AMP on cell Ca distribution and the kinetics of Ca exchange. The overall aim is to (1) characterize the mechanisms responsible for cyclic AMP-induced Cl secretion by rabbit colon; (2) elucidate the role of Na in this process, especially with regard to the role of Na transport in the energetics of Cl secretion; and (3) provide a critical appraisal of the role of intracellular Ca as a mediator of the secretory response. The results of these studies should provide a basis for the understanding of secretory processes of a variety of epithelial tissues and should provide insight into the mechanisms responsible for salt and water losing enteropathies.